Characterizing 1341 cases of veterinary toxicoses confirmed in western Canada: A 16-year retrospective study

Abstract

Veterinary toxicoses are frequently observed in western Canada. This study reports the frequency and characteristics of intoxications in animals reported between January 1, 1998 and December 31, 2013. Information was obtained from toxicological case records from the Prairie Diagnostic Services, Saskatoon, Saskatchewan. There were 1341 animal poisonings with 19 compounds over the investigational period. Lead poisoning was the most common toxicity (43.7%). Poisoning with acetylcholinesterase inhibitors and strychnine were also common events. Poisonings were most common in 2001, 2009, and 2012. Intoxications occurred most frequently during the months of May through July. Cattle were the most commonly poisoned species (n = 696), followed by dogs and eagles.

Introduction

Domestic and wildlife animal poisonings are common in western Canada (1). The vast array and availability of compounds used in industry and agriculture, feed nutrition and ration formulation, and environmental contamination all contribute to annual poisonings. In conjunction with veterinary medical intervention in the diagnosis of animal poisonings, diagnostic laboratories are often employed to perform analytical testing to determine a cause of sickness or death. The diagnostic case records from such laboratories have informed the medical community of the epidemiology of these poisonings. Causative agents, annual frequency, temporal frequency, and species affected can all be determined using toxicological case record data. This information can be used to infer the use of a toxic agent (e.g., spraying of agricultural pesticides or use of essential mineral nutrients in feed), the misuse of a toxic agent (e.g., strychnine baiting for off-label use), and the presence of contamination in the immediate or greater environment of the animals (e.g., lead batteries on pasture grazed by cattle). Epidemiologic information acquired from these records may inform veterinarians, livestock producers, and farmers in animal management and husbandry, and government agencies involved in surveillance and regulation. The purpose of this study was to report the frequency and characteristics of veterinary intoxications in western Canada diagnosed by the Prairie Diagnostic Services diagnostic toxicological laboratory between January 1, 1998 and December 31, 2013.

Materials and methods

Poisoning events from case records received by Prairie Diagnostic Services (Western College of Veterinary Medicine, Saskatoon, Saskatchewan) between January 1, 1998 and December 31, 2013 were identified and compiled. Toxic agent, animal species affected, month of poisoning, and year of poisoning were tabulated. Percent occurrence for all of these variables was calculated. Toxic agents that were reported in less than 20 cases were grouped together into an “other” category.

Analytical equipment used by Prairie Diagnostic Services changed throughout the investigational period. Metals (Cu, Zn, Mg, Fe, Mn, Mo, Se, Co, Be, V, Cr, Ni, As, Sr, Cd, Sn, Sb, Ba, Tl, Pb, and Bi) in liver and kidney tissues were quantified through nitric acid digestion and inductively coupled plasma mass spectrometry (ICP-MS) analysis (Thermo Jarrel Ash Corporation, Franklin, Massachusetts, USA). Whole heparinized blood lead concentrations were determined with LeadCare I or LeadCare II instrumentation through Aniodic Stripping Voltammetry (Magellan Diagnostics, Chelmsford, Massachusetts, USA). Trace mineral and metal toxicity was diagnosed using the parameters described by Puls (2). Vitamins A and E (retinol, tocopherol) in plasma, serum, and tissue were quantified by high performance liquid chromatography (HPLC) and spectrophotometric methods using the instrument software (Waters 2996 PDA System 1500 series; Milford, Massachusetts, USA) (3). Strychnine was quantified in blood, stomach contents, liver, and vomitus by chloroform/sulfuric acid extraction and spectrophotometric methods (λ = 255 nm) (4). Brain acetyl-cholinesterase activity was used as a surrogate for toxic acetyl-cholinesterase inhibitor (i.e., organophosphate or carbamate insecticide) exposure. Toxicity was confirmed using the values indicated by Blakley and Yole (5). A modification of the Ellman colorimetric detection method was used for brain acetylcholinesterase analysis (5–7). Nitrite concentration in serum and ocular fluid and whole heparinized blood methemoglobin content (by percentage) were determined using spectrophotometric techniques (λ = 635 nm) (8). Dicoumarol concentration in liver tissue was quantified by thin-layer chromatography (TLC); this method has since been phased out at Prairie Diagnostic Services. Metaldehyde toxicity was confirmed using distillation and spectrophotometric analysis and has since been phased out by Prairie Diagnostic Services.

Statistical significance for no-observed difference in annual or temporal incidence was determined by Chi-square analysis (P < 0.01). Chi-square analysis was conducted for the overall profile of toxic agents and selected individual agents that were the most numerous (lead, acetylcholinesterase inhibitors, strychnine).

Results

Toxicological case records identified 1341 poisoning events from 1998 to 2013. Nineteen agents in 6 major classifications of compounds were associated with the observed toxicoses (Table 1). Lead poisoning was the most common toxicity and comprised 43.6% of the total cases (Table 2). Acetylcholinesterase inhibitor pesticide and strychnine rodenticide cases were also common (20.8% and 10.5% of reported cases, respectively). Other toxic agents identified in the poisoning events are listed in Table 2 and categorized in Table 1. Toxic metal poisoning (Pb, Cd, Hg, As) accounted for most of the observed toxicities (44.1%) (Table 1). Pesticide poisonings (including insecticides, rodenticides, and molluscicides) were 31.4% of the total cases. Toxicity from trace minerals/essential metals (Cu, Se, Fe, Mo, Mn, Mg, Zn, and Na) occurred in 22% of the cases.

Table 1.

Classes of compounds in veterinary toxicoses confirmed by Prairie Diagnostic Services in western Canada from 1998 to 2013

Class of compound	Number of cases	%
Toxic metalsa	592	44.1
Pesticidesb	421	31.4
Essential metalsc	295	22.0
Hemoglobin oxidizing agents	14	1.0
Toxic plantsd	10	0.7
Vitamins (A, E)	9	0.7
Total	1341	100.0

^aPb, Cd, Hg, As.

^bInsecticides (acetylcholinesterase inhibitor); rodenticides (strychnine); molluscicides (metaldehyde).

^cCu, Se, Fe, Mo, Mn, Mg, Zn, and Na.

^dSweet clover (dicoumarol) and plants containing cyanogenic glycosides.

Table 2.

Overall profile of confirmed veterinary toxicoses by Prairie Diagnostic Services in western Canada from 1998 to 2013^a,^b

Toxic agent	Number of cases	%
Lead	585	43.6
Acetylcholinesterase inhibitors	279	20.8
Strychnine	141	10.5
Copper	122	9.1
Selenium	82	6.1
Molybdenum	25	1.9
Iron	20	1.5
Sodium	19	1.4
Nitrite (methemoglobin formation)	14	1.0
Manganese	10	0.7
Zinc	11	0.8
Vitamin (A, E)	9	0.7
Dicoumarol	8	0.6
Magnesium	6	0.4
Arsenic	4	0.3
Cyanide	2	0.1
Mercury	2	0.1
Cadmium	1	0.1
Metaldehyde	1	0.1
Total	1341	100.0

^aMean annual occurrence = 83 cases (range: 46 to 143).

^bMean monthly occurrence = 111 cases (range: 41 to 198).

Poisoning events occurred annually (Table 3). The mean case frequency on an annual basis was 83. Frequency of poisonings was highest in the years 2009 (n = 143), 2001 (n = 126), and 2012 (n = 114). The Chi-square probability of no annual difference of poisoning with all agents was P < 0.0001. Incidence of lead poisoning was highest in 2009 (n = 84). Incidence of strychnine poisoning was highest in 2001 (n = 22). Incidence of poisoning with acetylcholinesterase inhibitors was highest in 2006 (n = 31). The individual Chi-square probabilities of no annual difference for lead, acetylcholinesterase inhibitors, and strychnine were all P < 0.0001.

Table 3.

Annual occurrence of animal poisonings in western Canada confirmed by Prairie Diagnostic Services from 1998 through 2013^a

Toxic agent	1998	1999	2000	2001	2002	2003	2004	2005	2006	2007	2008	2009	2010	2011	2012	2013
Leadb	39	33	29	66	27	35	19	20	54	31	24	84	41	27	31	25
Acetylcholinesterase inhibitorsb	9	14	26	25	23	16	24	18	31	26	1	11	11	18	15	11
Strychnineb	10	7	17	22	9	5	12	1	3	2	4	7	15	8	13	6
Copper	3	1	3	6	3	7	0	7	0	5	5	15	9	11	31	16
Selenium	1	1	2	1	2	1	6	3	6	3	3	15	10	5	18	5
Molybdenum	0	0	2	0	17	0	0	0	0	0	1	0	0	1	2	2
Iron	1	0	0	0	5	1	1	1	2	1	1	3	0	0	4	0
Sodium	1	0	1	1	0	0	0	2	1	2	4	1	1	3	0	2
Othere	6	6	3	5	5	3	3	6	2	1	3	7	4	4	0	10
Total	70	62	83	126	91	68	65	58	99	71	46	143	91	77	114	77

^aThe probability of no year effect for all toxic agents was P < 0.0001.

^bThe probability of no year effect for each of lead cases, acetylcholinesterase inhibitor cases, and strychnine cases was P < 0.0001.

^cOther: 1998 (3 dicoumarol, 1 nitrite, 2 vitamin); 1999 (3 dicoumarol, 1 Mn, 1 Mg, 1 As); 2000 (1 metaldehyde, 2 vitamin); 2001 (1 dicoumarol, 1 nitrite, 2 Zn, 1 vitamin); 2002 (1 dicoumarol, 1 Mn, 1 Mg, 1 As, 1 CN); 2003 (2 nitrite, 1 Zn); 2004 (1 nitrite, 1 Zn, 1 CN); 2005 (4 nitrite, 1 Zn, 1 Hg); 2006 (1 nitrite, 1 Mg); 2007 (1 vitamin); 2008 (1 Mn, 2 As); 2009 (1 Zn, 3 Mg, 2 vitamin, 1 Hg); 2010 (1 nitrite, 2 Zn, 1 Mn); 2011 (3 Mn, 1 vitamin); 2013 (3 nitrite, 3 Zn, 3 Mn, 1 Cd).

Case submissions were most common in the months of May (n = 198), July (n = 196), and June (n = 175) (Table 4). The mean monthly poisoning occurrence was 111. The Chi-square probability of no month effect of poisoning with all agents was P < 0.0001. Lead poisoning occurred most frequently in July (n = 132), June (n = 115), and May (n = 94). Strychnine poisoning occurred most frequently in March (n = 22), September (n = 20), and October (n = 10). Acetylcholinesterase inhibitor poisoning occurred most frequently in May (n = 57), April (n = 38), and July (n = 27). The individual Chi-square probabilities of no monthly difference for lead, acetylcholinesterase inhibitors, and strychnine were all P < 0.0001.

Table 4.

Monthly occurrence of animal poisonings confirmed by Prairie Diagnostic Services from 1998 through 2013^a

Toxic agent	Jan	Feb	March	April	May	June	July	Aug	Sept	Oct	Nov	Dec
Leadb	43	9	25	42	94	115	132	23	14	29	42	17
Acetylcholinesterase inhibitorsb	19	12	19	38	57	24	27	12	11	15	19	26
Strychnineb	2	6	22	14	15	5	13	7	20	18	10	9
Copper	16	5	12	16	10	12	14	15	5	6	7	4
Selenium	2	4	19	23	13	5	3	1	6	5	0	1
Molybdenum	0	0	1	2	0	1	0	1	2	16	2	0
Iron	3	1	0	1	1	1	4	1	3	3	1	1
Sodium	0	0	0	3	1	6	0	2	0	5	2	0
Otherc	7	4	8	10	7	6	3	2	3	4	8	6
Total	92	41	106	149	198	175	196	64	64	101	91	64

^aThe probability of no month effect for all toxic agents was P < 0.0001.

^bThe probability of no month effect for each of lead cases, acetylcholinesterase inhibitor cases, and strychnine cases was P < 0.0001.

^cOther: January (1 dicoumarol, 3 Zn, 3 vitamin); February (1 metaldehyde, 1 Mn, 1 Mg, 1 vitamin); March (2 dicoumarol, 1 Zn, 4 Mn, 1 vitamin); April (1 dicoumarol, 2 nitrite, 2 Zn, 1 Mn, 2 As, 2 vitamin); May (1 Zn, 1 Mn, 1 Mg, 2 As, 2 vitamin); June (4 nitrite, 1 Mg, 1 Hg); July (1 nitrite, 1 Zn, 1 CN); August (1 Zn, 1 CN); September (1 nitrite, 1 Mn, 1 Cd); October (1 dicoumarol, 2 nitrite, 1 Zn); November (1 dicoumarol, 4 nitrite, 1 Mn, 1 Mg, 1 Hg); December (2 dicoumarol, 1 Zn, 1 Mn, 2 Mg).

Cattle were the most commonly poisoned animal species (n = 696) (Table 5). Poisonings in cattle were attributed to lead (525 cases), selenium (58 cases), copper (30 cases), and molybdenum (19 cases). Lead poisoning comprised 75.4% of the total cattle poisonings. Other poisoning events in cattle included nitrite toxicity (13 cases), salt poisoning (12 cases), and sweet clover/dicoumarol poisoning (7 cases).

Table 5.

Profile of cattle poisonings confirmed by Prairie Diagnostic Services, Saskatoon, Saskatchewan from 1998 through 2013

Toxic agent	Number of toxic events	%
Lead	525	75.4
Selenium	58	8.3
Copper	30	4.3
Molybdenum	19	2.7
Acetylcholinesterase inhibitors	15	2.2
Nitrite/methemoglobin	13	1.9
Sodium salt	12	1.7
Dicoumarol	7	1.0
Vitamins (A, E)	6	0.9
Arsenic	3	0.4
Iron	3	0.4
Zinc	3	0.4
Manganese	1	0.1
Cyanide	1	0.1
Total	696	100.0

Copper was the primary source of toxicity for the combined ovine and caprine species (n = 62) (Table 6). Sheep and goats, collectively, were the second most frequently poisoned livestock species.

Table 6.

Profile of sheep and goat poisonings confirmed by Prairie Diagnostic Services, Saskatoon, Saskatchewan from 1998 through 2013

Toxic agent	Number of cases	%
Copper	62	62
Selenium	17	17
Manganese	9	9
Magnesium	3	3
Molybdenum	2	2
Vitamins (A, E)	2	2
Acetylcholinesterase inhibitors	1	1
Dicoumarol	1	1
Nitrite/methemoglobin	1	1
Iron	1	1
Zinc	1	1
Total	100	100

The number of dog poisonings over the investigational period was 139. Dogs represented the second most commonly poisoned animal species during the investigational period (Table 7). Strychnine (93 cases), acetylcholinesterase inhibitors (19 cases), and copper (16 cases) comprised the majority of the agents in canine toxicities.

Table 7.

Profile of dog poisonings confirmed by Prairie Diagnostic Services, Saskatoon, Saskatchewan from 1998 through 2013

Toxic agent	Number of cases	%
Strychnine	93	66.9
Acetylcholinesterase inhibitors	19	13.7
Copper	16	11.5
Zinc	4	2.9
Lead	3	2.2
Sodium salt	2	1.4
Iron	1	0.7
Metaldehyde	1	0.7
Total	139	100.0

Eagles were the most commonly poisoned wildlife species (Table 8). The 117 poisonings occurred in the bald eagle (Haliaeetus leucocephalus) and the golden eagle (Aquila chrysaetos). Poisoning with acetylcholinesterase inhibitors was the most common toxicity in eagles (55.6% cases). Lead (42 cases), strychnine (9 cases), and mercury (1 case) were other causes of intoxication.

Table 8.

Profile of eagle poisonings confirmed by Prairie Diagnostic Services, Saskatoon, Saskatchewan from 1998 through 2013

Toxic agent	Number of cases	%
Acetylcholinesterase inhibitors	65	55.6
Lead	42	35.9
Strychnine	9	7.7
Mercury	1	0.9
Total	117	100.0

Discussion

Lead poisoning was the most common heavy metal toxicity and the most common toxicosis in cattle over the investigational period. These observations are widely accepted and are comparable to other Canadian retrospective studies (1,9). A 5-year retrospective study in Ontario, Canada, reported that approximately 45% of positive diagnoses of metal toxicities were associated with lead and cattle constituted 72.9% of animals poisoned with lead (9). These values are similar to those found in the present study. Lead poisoning in cattle appears to be more common in western Canada, likely due to the prevalence of livestock-based agriculture in western Canada. In the Ontario study, the authors reported that cattle were also found to be poisoned with copper, zinc, and iron (9). In the present study, selenium, copper, and molybdenum intoxications were also observed in cattle.

Despite homeostatic mechanisms that regulate trace mineral concentrations, cattle may become poisoned with these elements through dietary sources. Selenium poisoning in cattle can originate from grazing of highly seleniferous plants and soils. Point sources of selenium in agriculture include bactericides, fungicides, and herbicides (10,11). Selenium injectables for veterinary use also represent an important point source. Organic selenium, the form used in agricultural pesticide formulations, appears to be more toxic to cattle and ruminants in general compared to inorganic selenium (11). Incomplete or absent case histories prevented identification of the source of selenium toxicity in the present study. Trace mineral interactions likely played a role in the observed toxicities. An example of this is molybdenum toxicity as the cause of conditioned copper deficiency (12). Molybdenum toxicity was responsible for a number of cattle toxicities in the present study. Cattle are the least tolerant livestock species to high dietary molybdenum (12), which appears to be reflected in the data in the current study. It is unclear whether or not the animals poisoned with molybdenum were experiencing hypocuprosis; however, it should be considered in ruminant management practices.

In a study of diagnostic case records from the province of Saskatchewan from 1968 to 1982, lead toxicosis was a predominant animal intoxication (1). In agreement with the current study and that of Hoff et al (9), cattle were the species most commonly affected with lead poisoning (86.5% of recorded lead poisoning cases) (1). The results from 1968 through 1982, along with those of the current study suggest that lead poisoning in cattle has been the most common veterinary toxicosis in western Canada (Alberta, Saskatchewan, and Manitoba) for the past 4 decades. Blakley (1) also reported that cattle often became poisoned with dicoumarol (36 cases) and nitrite (8 cases). Cattle poisonings with these compounds were observed over the 16-year period of the present study, but occurred at a relatively low frequency. Changing pasture management and the reduced production of crops containing dicoumarol or nitrite contaminants may have contributed to the decline in toxicoses.

Dogs were the second most frequently poisoned animal species. This is consistent with the findings of Blakley (1). In that study (1), dogs accounted for almost 92% of all strychnine poisonings from 1968 through 1982. In the present study, the percentage of dogs poisoned with strychnine appeared to have decreased. Almost 3 times as many dogs (n = 261) were poisoned with strychnine in the previous Blakley study (1) compared to the present study. This decline is likely due to the more stringent regulations on the access to strychnine and the compliance with the use of strychnine (13). The labelled-use for strychnine in Canada is for control of pocket gophers and Richardson’s ground squirrels (13–15). The recommended time of year to place strychnine-laced baits is the early spring (14). This is consistent with the high incidence of poisoning with strychnine in March. The incidence of strychnine poisoning reported in the prior Blakley study was highest in February, March, and April for all species (1). The high frequency of cases in September and October suggests off-label or malicious use. A 10-year study of sudden death in dogs from 1989 to 1999 in Saskatchewan described toxicity as the second leading cause of death, following heart disease (16). Considering the 25 cases of toxicity-related sudden deaths reported, strychnine poisoning accounted for 24 (or 96%) of these cases. Strychnine poisoning, although declining, remains a concern for dog owners and veterinarians.

In contrast to the findings for strychnine, an epidemiologic study using information gathered by the American National Poison Data System from 2000 to 2010 described long-acting anticoagulant rodenticides as the major cause of death in dogs (17). This was followed by “unknown” rodenticides and carbamates. Prairie Diagnostic Services does not conduct tests for long-acting anticoagulant rodenticides, such as brodifacoum and diphacinone. The addition of these compounds to the diagnostic testing repertoire may be reasonable considering the information described in the study by Buttke et al (17). It should be noted that local or regional restrictions or use patterns throughout North America may also contribute to the discrepancies among these studies.

The Ontario study (9) did not document toxicities in addition to metals and thus did not describe the incidence of strychnine poisoning (9). However, dogs which accounted for 133 of the 887 cases of metal toxicosis were found to be poisoned with copper, lead, and zinc (9). In contrast to these results, lead poisoning was uncommon for dogs in the present study. This may reflect differences in industrial or domestic (paint, plumbing) sources of lead between the 2 regions and local (water) contamination issues. However, many copper and zinc poisoning cases were observed. Copper poisoning in dogs appears to be related to a genetic predisposition to hepatitis in many instances (9). For example, terrier species may have impaired copper excretion relating to an inherited metabolic dysfunction (18). Other species may be subject to copper accumulation due to chronic cholestasis from primary inflammatory hepatic disease (18). Zinc poisoning in dogs is often the result of ingestion of zinc-containing metallic objects, e.g., coins, or consumer products with high zinc content, e.g., zinc diaper ointment (19,20).

Copper toxicity was responsible for most of the poisonings observed in sheep and goats. These animals were considered as a group due to a similar phylogeny. However, sheep appear to be more sensitive to dietary copper exposure than goats (21). One study investigating copper toxicity in lambs and goats indicated that liver copper storage was 6 to 9 times greater in lambs than in goats (21). Sheep are unable to enhance copper excretion in response to increasing copper body burdens (22).

The bald eagle (Haliaeetus leucocephalus) and the golden eagle (Aquila chrysaetos), were the most frequently poisoned wildlife species. The predilection of eagles, especially the bald eagle, for scavenging of carcasses may explain this result (23). Poisonings with acetylcholinesterase inhibitor insecticides and lead were prevalent. Poisoning of raptor species with organophosphate and carbamate agents has been reported previously in Canada (24,25). Eagles may become exposed to this class of pesticides through multiple routes, including relay toxicity, in which the eagle is poisoned through ingestion of a poisoned animal or toxic carrion (24,25). Secondary toxicity also appears to be a major mechanism of exposure of eagles to lead. Lead poisoning in eagles has been shown to originate from consumption of contaminated game animals killed by lead shot. Carcasses and entrails left on-site by hunters may be scavenged by eagles (26). Richardson’s ground squirrels killed by hunters’ lead shots have been demonstrated to be a source of lead for scavenging hawks (27) and may also be of risk to eagles. Strychnine, licensed for Richardson’s ground squirrel control, was responsible for a small portion of poisoning events in eagles. This may suggest that eagles scavenge on rodents killed as part of pest-control efforts. Non-target poisoning of eagles with pesticides and lead appears to be related to scavenging of toxic carcasses and carrion. This remains a substantial wildlife conservation concern.

Poisoning with acetylcholinesterase inhibitor compounds (i.e., organophosphate and carbamate insecticides) was commonly observed during the period of this study. This is contrary to the results of Blakley (1), in which acetylcholinesterase inhibitor pesticide poisonings accounted for only 24 of the total cases (1). This difference may be related to increased wildlife carcass submission, increased public interest, greater regulatory presence, increased use of these agents, or a greater availability of diagnostic testing services. The exposure data in the case records in the present study did not allow us to determine whether poisoning was accidental or malicious. However, the high temporal incidence of the cases generally coincides with intense agricultural activities. This may be indicative of poisoning due to spray drift or ingestion of contaminated feed and water. Regardless, non-target toxicity occurred in greater numbers in wildlife, livestock, and companion animals.

As indicated in the Blakley study (1), chlorinated compounds were implicated in 58 of the 990 cases reported from 1968 to 1982. This reflects a historical contamination issue; organochlorine pesticides were in use during the late 1960s and early 1970s but have since been banned in Canada. Acetylcholinesterase inhibitor pesticides entered the North American market following the ban to meet the demands of agricultural development. The increase in poisoning with acetylcholinesterase inhibitor agents is likely a reflection of the replacement of the chlorinated pesticides with these agents.

There were no reported cases of warfarin or trichothecene mycotoxin poisonings (1). Limited crop contamination with mycotoxins accounted for the latter observation. Mercury and metaldehyde poisoning were more prevalent from 1968 and 1982 and have declined to a minimal occurrence from 1998 to 2013. The use of mercury as a seed treatment in agriculture has been banned. The dry field conditions during most of the study period likely limited the use of metaldehyde.

Over an extended period of time, it is evident that patterns associated with animal poisonings are influenced by changing environmental conditions, government regulations, testing capabilities, chemical availability, and husbandry practices. CVJ